Scanning Electron Micrograph of Streptococcus pneumoniae.: Streptococcus pneumoniae is a leading cause of serious illness among young children worldwide and is the most frequent cause of pneumonia, bacteremia, sinusitis, and acute otitis media (AOM). Widespread overuse of antibiotics contributes to emerging drug resistance. Photograph by courtesy of CDC

 Diseases/Pathogens Associated with Antimicrobial Resistance

A growing number of disease-causing organisms, also known as pathogens, are resistant to one or more antimicrobial drugs.  A wide range of pathogens—including the bacteria that cause tuberculosis, the viruses that causes influenza, the parasites that cause malaria, and the fungi that cause yeast infections—are becoming resistant to the antimicrobial agents used for treatment.  The link from  this title takes you to further information about some of the organisms and diseases associated with antimicrobial resistance. From the U.S. Centers for Disease Control and Prevention (CDC).

“The emergence of AMR [antimicrobial resistance] is a complex problem driven by many interconnected factors; single, isolated interventions have little impact. A global and national multi-sectoral response is urgently needed to combat the growing threat of AMR.” (WHO)

“A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill,” warned Dr. Margaret Chan, Director-General of the World Health Organization (WHO) in her address to the Combating Antimicrobial Resistance – Time for Joint Action conference held in Copenhagen, Denmark on 14 March 2012.

“If current trends continue unabated, the future is easy to predict,” Dr. Chan said. “Some experts say we are moving back to the pre-antibiotic era. No. This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry, especially for gram-negative bacteria. The cupboard is nearly bare.”

The Food and Drug Administration's (FDA's) Center for Veterinary Medicine (CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria.   Over time, the use of antimicrobial drugs will result in the development of resistant strains of bacteria, complicating clinician's efforts to select the appropriate antimicrobial for treatment.  Accordingly, efforts are underway in both veterinary and human medicine to preserve the effectiveness of these drugs. This and all FDA CVM produced material may be copied, reproduced, and distributed as long as FDA's Center for Veterinary Medicine is cited as the corporate author. Available on YouTube at http://youtu.be/AYvX8tnCM9s

“We would have much more success with bacteria if we weren’t so profligate with our best weapon against them: antibiotics”´ Bill Bryson writes in his book, A Short History of Nearly Everything. “Remarkably, by one estimate some 70 percent of the antibiotics  used in the developed world were given to farm animals, often routinely in feed stock, simply to promote growth or as a precaution against infection. Such applications give bacteria every opportunity to evolve a resistance to them. It is an opportunity that they have enthusiastically seized.

“In 1952, penicillin was fully effective against all strains of staphylococcus bacteria, to such an extent that by the early 1960s the US surgeon-general, William Stewart, felt confident enough to declare: ‘The time has come to close the book on infectious diseases. We have basically wiped out infection in the United States.’ Even as he spoke, however, some 90 per cent of those strains were in the process of developing immunity to penicillin. Soon one of these new strains, called methicillin-resistant staphylococcus aureus, began to show up in hospitals. Only one type of antibiotic, vancomycin, remained effective against it, but in 1997 a hospital in Tokyo reported the appearance of a strain that could resist even that.” 

The Combating Antimicrobial Resistance – Time for Joint Action conference brought together European Union Member States to explore what they can do to help solve the “serious, growing, and global threat to health addressed the challenges of AMR.” Best practices and solutions were discussed including the importance of improving data collection and surveillance, stopping the overuse of antibiotics, and reducing the use of the critically important antibiotics.

Get Smart about Antibiotics

You don't always need antibiotics when you're sick—only for infections caused by bacteria. And overuse is causing a global health problem. From the U.S. Food and Drug Administration, 15 November 2011.  Learn more at http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm092810.htm

“Drug-resistant pathogens are notorious globe-trotters"

Dr. Chan emphasized the widespread presence of drug-resistance saying that “Drug-resistant pathogens are notorious globe-trotters. They travel well in infected air passengers and through global trade in food. In addition, the growth of medical tourism has accelerated the international spread of hospital-acquired infections that are frequently resistant to multiple drugs.”

“At a time of multiple calamities in the world, we cannot allow the loss of essential antimicrobials, essential cures for many millions of people, to become the next global crisis,” remarked Dr. Chan.  

Dr. Chan spoke of the loss of “first-line antimicrobials” and said pointed out that “Replacement treatments are more costly, more toxic, need much longer durations of treatment, and may require treatment in intensive care units.”

“Some sophisticated interventions, like hip replacements, organ transplants, cancer chemotherapy, and care of preterm infants, would become far more difficult or even too dangerous to undertake,” Dr. Chan cautioned. “For patients infected with some drug-resistant pathogens, mortality has been shown to increase by around 50%.”

She provided an example of what this means for a disease of global significance: “Among the world’s 12 million cases of tuberculosis in 2010, WHO estimates that 650,000 involved multidrug-resistant TB strains. Treatment of MDR-TB [Multi-drug-resistant tuberculosis] is extremely complicated, typically requiring two years of medication with toxic and expensive medicines, some of which are in constant short supply. Even with the best of care, only slightly more than 50% of these patients will be cured.”

Methicillin-resistant Staphylococcus aureus (MRSA): This 2005 scanning electron micrograph (SEM) depicted numerous clumps of methicillin-resistant Staphylococcus aureus bacteria, commonly referred to by the acronym, MRSA; Magnified 9560x. Methicillin-resistant Staphylococcus aureus (MRSA) is a type of bacteria that is resistant to certain antibiotics. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin, and amoxicillin. Serious or life-threatening occurrences of "Staph" infections, including MRSA, occur most frequently among persons in hospitals and healthcare facilities (such as nursing homes and dialysis centers) who have weakened immune systems. Photograph by Janice Haney Car courtesy of CDC
 

“Many other pathogens are developing resistance to multiple drugs, some to nearly all,” Dr. Chan said. “Hospitals have become hotbeds for highly-resistant pathogens, like MRSA [Methicillin-resistant Staphylococcus aureus], ESBL[Extended-spectrum beta-lactamase], and CPE [carbapenamase-producing Enterobacteriaceae], increasing the risk that hospitalization kills instead of cures. These are end-of-the-road pathogens that are resistant to last-line antimicrobials.”

In the United States, preventing MRSA infections is a high priority for the Center for Disease Control and Prevention (CDC).  CDC says that the federal government uses several complementary systems to track drug-resistant infections and drug-resistant bacteria, including MRSA, in humans as well as in animals and food. In the effort, the National Antimicrobial Resistance Monitoring System (NARMS) is working in a collaboration among the CDC,  U.S. Food and Drug Administration Animal & Veterinary (FDA-CVM), and U.S. Department of Agriculture (USDA).

NARMS specifically targets drug resistance in bacteria more commonly associated with foodborne disease. Through the NARMS program, the FDA-CVM is currently conducting a pilot study to measure MRSA in meat items purchased from retail establishments.

Be Food Safe: Studies over many years have found antibiotic-resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), in a variety of food products including retail meats and raw milk. Photograph and text from the U.S. CDC.CDC reports that it is actively working to reduce MRSA infections in the United States through intensive efforts with healthcare providers to improve infection control practices and prevent Healthcare-associated Infections (HAI).

CDC also continually monitors the occurrence of MRSA and other infections in the population. CDC’s work provides the foundation for national and local healthcare-associated prevention efforts. 

• ·For more information visit CDC's MRSA website.
• ·For more information on preventing MRSA in community and healthcare settings please visit CDC's MRSA website and Preventing MRSA Infections in Healthcare Settings
• ·For more information on food safety, please visit foodsafety.gov.

While more study is needed to understand whether MRSA in foods and food animals plays a role in human infection, to date there have not been any documented cases of people getting MRSA from eating food that contains MRSA.  Rather, MRSA is usually spread directly from person to person. It is important to note that appropriate handling and cooking of raw meat should eliminate any risk of transmission to people.  Handling and cooking recommendations can be found at CDC's Be Food Safe.

A message about the use of antibiotics in meat production from Stephen McDonnell, founder and CEO of Applegate Farms.

Livestock Antibiotic Ban in the U.S. Next Steps

“The Obama administration must warn drug makers that the government may soon ban agricultural uses of some popular antibiotics that many scientists say encourage the proliferation of dangerous infections and imperil public health, a federal magistrate judge ruled on Thursday,” reported  Gardiner Harris in the New York Times on March 23, 2012.  

The order effectively restarts a process that the Food and Drug Administration began 35 years ago, but never completed, Harris writes.  The order was “intended to prevent penicillin and tetracycline, widely used antibiotics, from losing their effectiveness in humans because of their bulk use in animal feed to promote growth in chickens, pigs and cattle.”  

“The order comes two months after the Obama administration announced restrictions on agricultural uses of cephalosporins, a critical class of antibiotics that includes drugs like Cefzil and Keflex, which are commonly used to treat pneumonia, strep throat and skin and urinary tract infections.”

One Health Approach Advanced by ECDC

Prudent use of antibiotics is crucial, both in humans and in animals, stresses Marc Sprenger, Director, European Centre for Disease Prevention and Control  (ECDC) who presented the trends of AMR at the Combating antimicrobial resistance conference. He called for ‘one health' approach to tackle antimicrobial resistance problems in humans and animals.  "The problems of high antibiotic consumption levels in both humans and animals, and of AMR, cannot be solved in isolation. Animals and humans are one health. The European Commission advocates for the ‘One health’ aspect in order to tackle AMR. Prudent use of antibiotics is crucial, not only in humans but also in animals," he said.

A new report, The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food-borne Outbreaks in 2010, ECDC produced jointly with the European Food Safety Authority (EFSA) shows that resistance to several antimicrobials was commonly detected in zoonotic bacteria such as Salmonella and Campylobacter. "This report makes an important contribution to current work being carried out at EU-level to fight antimicrobial resistance," Sprenger said.

Limiting Consumption

Thanks to EU drug use surveillance, “we know that consumption patterns and resistance levels vary greatly across Europe, pointing to a clear need to share experiences and harmonize best practices,” Dr. Chan said.

Denmark and several other European nations have achieved low domestic antibiotic consumption, Dr. Chan said. This was accomplished “through multisectoral collaboration and a range of targeted measures.”   

“In particular, Denmark has tackled the problem of antibiotic use in food-producing animals in a pioneering way. Recognizing the potential for a health crisis, this country progressively ended the administration of antibiotics as growth-promoters in the late 1990s, well before the EU-wide ban. An international review panel… concluded that the ban reduced human health risks without significantly harming animal health or farmers’ incomes.

“In fact, Danish government and industry data showed that livestock and poultry production actually increased following the ban, while antibiotic resistance on farms and in meat declined.

“What began as the Danish “experiment” became the Danish ‘model.’”

“The termination of the use of antibiotics as growth promoters had a voluntary component on the part of industry, strongly motivated by consumer concerns, “Dr. Chan said.

Pharmaceuticals and Personal Care Products

Australian, Canadian and nations within the European Union are global leaders in “in terms of their proactive efforts in reducing the harmful effects of improper PPCP [pharmaceuticals and personal care products] disposal on human and environmental health by providing the legal framework and resources,” according to Danielle McDonald, Ph.D., in “Pharmaceuticals and Personal Care Products in the Environment,” in the book Water and Sanitation Related Diseases and the Environment: Challenges, Interventions, and Preventive Measures.

Limiting the consumption of pharmaceuticals to reduce the quantities present in the environment is an essential step, McDonald says, and proposes steps to do so:

·         To educate healthcare practitioners to ensure they fully understand the importance and environmental implications of selecting the right medication and therapy for each patient;

·         To identify the lowest effective dosage on a per person basis which requires that pharmaceuticals be packaged in small enough quantities to do so; and

·         To educate patients of the importance of completing treatments and following their physician’s directions precisely will ensure the proper dosing of pharmaceuticals and prevent the recurrence of illness due to improper pharmaceutical usage. 

The Director-General of the World Health Organization, Dr Margaret Chan, in a video statement to mark World Health Day 2011 and the theme, Combat Drug Resistance

The Director-General of the World Health Organization, Dr Margaret Chan, in a video statement to mark World Health Day 2011 and the theme, Combat Drug Resistance, has warned that "In the absence of urgent corrective and protective actions, the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated."  Available at http://youtu.be/DijWErm_wwU.  More information: ‪http://www.who.int/world-health-day/2011/en/index.htm.

In her “Combating Antimicrobial Resistance” conference speech Dr. Chan outlined several steps that are being taken in the EU:

·         A five-year action plan with twelve lines of action, underscoring the need for a broad-based, multi-pronged response. There is a strong convergence between these actions and those in WHO’s European strategic action plan on antibiotic resistance, launched last year. This sets the stage for many jointly-undertaken activities.

·         Last year, the WHO Regional Office for Europe also issued a guide to options for the prevention and containment of antibiotic resistance from a food safety perspective.

·         The EU is making good use of regulatory tools, and has solid technical backing from agencies like the European Food Safety Authority and the ECDC.

·         The EU has launched an unprecedented collaborative R&D effort to bring new antimicrobials to market.

·         The EU emphasizes the need to prevent infections in the first place, whether through vaccines or better hygiene, also in animals.

·         The EU new point-of-care diagnostic tools are another way to improve prescribing practices and promote prudent use.

·         The European Antibiotic Awareness Days keep the public alert to the threat and their role in diminishing it.

Worldwide, WHO is engaged in guiding the response to AMR through:

• policy guidance, support for surveillance, technical assistance, knowledge generation and partnerships, including through disease prevention and control programmes;
• essential medicines quality, supply and rational use;
• infection prevention and control;
• patient safety; and
• laboratory quality assurance.

The evolving threat of antimicrobial resistance

- Options for action

The evolving threat of antimicrobial resistance - Options for actionAs “a follow-up to last year’s World Health Day, on antimicrobial resistance, WHO has just launched a new document setting out options for action to combat antimicrobial resistance,” Dr. Chan announced.  

This publication, "The evolving threat of antimicrobial resistance - Options for action,” describes examples of policy activities that have addressed Antimicrobial resistance (AMR) in different parts of the world. Its aim is to raise awareness and to stimulate further coordinated efforts. 

“As that document notes,” Dr. Chan said, “much can be done to limit selective pressure on bacteria to develop resistance.  Namely: Prescribe antibiotics appropriately and only when needed. Follow treatment correctly. Restrict the use of antibiotics in food production to therapeutic purposes. And tackle the problem of substandard and counterfeit medicines.”

Successful strategies and measures highlighted are:

·         In Thailand, the "Antibiotic Smart Use" programme reduces the prescribing of and demanding for antibiotics by both prescribers and patients. It showed an 18%–46% reduction in antibiotic use while 97% of targeted patients recovered or improved regardless of whether they had taken antibiotics.

·         A program in pharmacies in Viet Nam consisting of inspection for prescription-only drugs, education on pharmacy treatment guidelines, and group meetings of pharmacy staff resulted in a significant reduction in antibiotic dispensing for acute respiratory infections.

Following health sector reforms in Viet Nam in the late 1990s, private pharmacies became increasingly important sources of health-care delivery. Major public health problems such as sexually transmitted diseases and acute respiratory infections are treated with antibiotics regularly dispensed without prescriptions, often inappropriately.

A study of antimicrobial use was conducted in Hanoi from 1997 to 2000.  Among a total of 789 private pharmacies in the urban area, 68 were randomly selected and assigned to control or intervention groups. The intervention package consisted of three parts: regulation enforcement with inspection for prescription-only drugs; face-to-face education on pharmacy treatment guidelines; and group meetings of pharmacy staff. After the intervention, practices were monitored using a simulated client method and improvements were identified: there were significant reductions in antibiotic dispensing for acute respiratory infections, and dispensing of cefalexin without prescription decreased from 95% to 56%. Interventions of this type could have a significant impact, considering the high level of utilization of private pharmacy services by those seeking health care in Viet Nam.

·         In Norway, the introduction of effective vaccines in farmed salmon and trout together with improved fish health management reduced the annual use of antimicrobials in farmed fish by 98% between 1987 and 2004.

·         In 2010, the University of Zambia School of Medicine revised their undergraduate medical curriculum. The topics of AMR and rational use of medicines were inserted prominently. The aim is that graduates enter clinical practice with the right skills and attitudes to be both effective practitioners and committed stewards of AMR containment.

·         A new Swedish government initiative for improving the use of antibiotics

Incentives to encourage rational use at several levels in the health-care system are important. In 2010, the Swedish government announced a strong financial commitment to improve the use of antibiotics. That year, the average use of antibiotics in outpatient care in Sweden was 390 prescriptions per 1000 inhabitants. A new national target was set: a maximum of 250 prescriptions per 1000 inhabitants per year to be reached by 2014. Annual rewards would be shared between those of the 21 county councils that had formed a multidisciplinary working group with a clear mandate to coordinate local activities according to the model proposed by the Swedish Strategic Programme against Antibiotic Resistance (Stramac)96 Participants were to increase the level of compliance with treatment recommendations and reduce the numbers of prescriptions for antibiotics in accordance with annual targets.

·         In a recent review, a total of 22 public education campaigns to promote a more prudent use of antibiotics at national or regional levels in high-income countries between 1990 and 2007 were identified and the characteristics and outcomes evaluated. The campaigns were distributed in Europe (16), North America (3), Oceania (2), and Israel (1).

In the USA, the Get Smart program included more than 30 different regional campaigns. In most cases, the campaigns were part of a national strategy to reduce antimicrobial use. All campaigns focused mainly on respiratory tract infections and education was mostly symptom-oriented. The intensity of the campaigns varied widely, from simple use of internet distribution channels to expensive mass-media campaigns. Most campaigns that were formally evaluated appeared to reduce antibiotic use. However, the impact on AMR could not be assessed from the data available.

 Proper Disposal of Antimicrobial Medicines

Microorganisms in Water: The need to address the problem of antibiotic-resistant bacteria present in wastewater

 “Beyond fungi, protozoa, viruses, algae, and susceptible bacteria, wastewater can serve as an important reservoir of antibiotic-resistant bacteria and their associated resistance genes,” writes  Amy R. Sapkota** in her chapter “Other Water Pollutants: Antibiotic-Resistant Bacteria,” in the book Water and Sanitation Related Diseases and the Environment: Challenges, Interventions, and Preventive Measures.  “Studies conducted in the United States, Europe, Asia, and other countries have documented elevated levels of antibiotic-resistant commensal and pathogenic bacteria in both untreated and treated wastewater present at various stages within wastewater treatment plants (WWTP). These organisms and their antibiotic resistance genes enter wastewater treatment plants WWTPs in wastewater originating from a variety of point and nonpoint sources including private homes, hospitals, pharmaceutical manufacturers, agricultural runoff, and urban runoff.

Related Links

·         WHO Fact Sheet on AMR

·         World Health Day – 7 April 2011  

·         More about antimicrobial resistance

·         Successful strategies to safeguard medications

·         10 facts on antimicrobial resistance

·         Unapproved Animal Drugs The U.S.FDA has serious concerns about unapproved  animal drugs. These drugs are not reviewed by FDA and may not meet FDA’s strict standards for safety and effectiveness.

·         The Alliance for the Prudent Use of Antibiotics (APUA)

• A Public Health Action Plan to Combat Antimicrobial Resistance: Surveillance (2001)
• Surveillance for Emerging Antimicrobial Resistance Connected to Healthcare (S.E.A.R.C.H.)
• Antibiotic Resistance Surveillance Toolkit for Streptococcus pneumoniae
• Intensive Care Antimicrobial Resistance Epidemiology (ICARE)
• Assisting Countries to Establish Antimicrobial Surveillance (WHO)
• The European Antimicrobial Resistance Surveillance System (EARSS)

·     Public Health Action Plan
In 2001, the Interagency Task Force on Antimicrobial Resistance developed A PublicHealth Action Plan to Combat Antimicrobial Resistance Part 1: Domestic Issues  [PDF - 261 KB] as a blueprint for specific, coordinated federal actions to address the emerging threat of antimicrobial resistance. Progress on implementation of the Action Plan is reported on a yearly basis in Annual Reports.

·     U. S. National Institutes of Health  Fact Sheet, Antimicrobial Resistance

• A Public Health Action Plan to Combat Antimicrobial Resistance: Surveillance (2001)
• Surveillance for Emerging Antimicrobial Resistance Connected to Healthcare (S.E.A.R.C.H.)
•  Antibiotic Resistance Surveillance Toolkit for Streptococcus pneumoniae
• Intensive Care Antimicrobial Resistance Epidemiology (ICARE)
• Assisting Countries to Establish Antimicrobial Surveillance (WHO)
• The European Antimicrobial Resistance Surveillance System (EARSS)

• Transatlantic Task Force on Antimicrobial Resistance (TATFAR)

• Diseases/Pathogens Associated with Antimicrobial Resistance

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